Plasmids are among the most useful vectors for cloning homologous or foreign genes in microorganisms. Recombinant DNA technology commonly utilizes these extrachromosomal elements for the isolation and characterization of specific genes, and for the expression of gene products. A great deal of effort has gone into the development of genetically engineered plasmid vectors for the gram-negative organism, Escherichia coli, as well as gram-positive organisms, such as Bacillus subtilis and Streptomyces lividans.
Difficulties have been encountered in transforming plasmids between unrelated species because of narrow host range origins of replication, restriction barriers, or unexpressed drug resistance markers. Thus the best starting point for recombinant DNA vector development is from naturally occurring plasmids from the same or closely related species. The present inventors have been able to isolate plasmids which can be useful vectors for applying recombinant DNA technology to the Actinomadura. Therefore, it is now possible to modify antibiotic producing Actinomadura species to increase antibiotic yield. In addition, it is possible to increase the yields of known antibiotics or to construct hybrid antibiotics by using this important class of microorganisms. In copending application Ser. No. 07/069,330 filed July 2, 1987, there are disclosed specific uses for the plasmids of the present invention. The text of that application is incorporated by reference.